Skip to main content
Log in

Immunomodulating activity in supernatants from EBV immortalized lymphocytes

  • Original Articles
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Summary

Our earlier work has demonstrated that EBV immortalized B lymphocytes are involved in a factor dependent autostimulatory cycle. Soluble growth stimulating activity was released into culture supernatants by these growing B cells. Growth enhancing (GE) media from B lymphocyte lines, immortalized by EBV infection, contained soluble factor(s) which modulated the Con A response of normal human mononuclear cells. Conditioned media from these lines affected the Con A response in a biphasic manner, stimulating the blastogenic response at lower concentrations, while inhibiting at higher concentrations. At stimulatory concentrations, the blastogenic response to Con A began earlier than in controls and was markedly enhanced by day 2. GE media reduced the initial response of purified B cells to pokeweed mitogen. GE media did not support growth of IL-2 dependent cells. GE media from some EBV-carrying B cell lines had measurable IL-1 activity in the mouse thymocyte PHA response. GE media from LPS stimulated B lymphocyte lines produced significant IL-1-like effects on stimulated mouse thymocytes. These results suggested that these B cell lines may produce IL-1-like factors that cooperate in T cell responses. The possibility that such factors may play a role in B lymphocyte transformation by EBV is discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bach FH, Alter BJ, Widmer MB, Segal M, Dunlap B (1981) Cloned cytotoxic and non-cytotoxic lymphocytes in mouse and man: their reactivities and a large cell surface memebrane protein (LMP) differentiation marker system. Immunol Rev 54:5

    Google Scholar 

  2. Beneke J, Pearson GR (1980) Inhibitors of DNA synthesis produced by Herpesvirus transformed cell lines. J Immunol 124:2944

    Google Scholar 

  3. Blazar BA, Sutton LM, Strome M (1983) Self-stimulating growth factor production by B-cell lines derived from Burkitt's lymphomas and other lines transformed in vitro by Epstein-Barr Virus. Cancer Res 34:4562

    Google Scholar 

  4. Boyum A (1968) Isolation of mononuclear cells and granulocytes from human blood. Isolation of mononuclear cells by one centrifugation and of granulocytes by combining centrifugation and sedimentation. Scand J Clin Lab Invest (Suppl.) 21:77

    Google Scholar 

  5. DeLarco JE, Todaro GJ (1978) Growth factors from murine sarcoma virus transformed cells. Proc Natl Acad Sci 75:4001

    Google Scholar 

  6. Depper JM, Leonard WJ, Kronke M, Waldmann TA, Greene WC (1984) Augmented T cell growth factor receptor in HTLV-1 infected human Leukemic T cells. J Immunol 133:1691

    Google Scholar 

  7. DiPersio JF, Brennan JK, Litchman MA, Speiser BL (1978) Human cell lines that elaborate colony stimulating activity for the marrow cells of man and other species. Blood 51:507

    Google Scholar 

  8. Doolittle RF, Hunkapiller MW, Hood LE, DeWare SG, Robbins KC, Aaronson SA, Antoniades HN (1983) Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science 221:275

    Google Scholar 

  9. Downard J, Yarden Y, Mayes E, Scrace G, Totty N, Stockwell P, Ullrich A, Schlessinger J, Waterfield MD (1984) Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature 307:521

    Google Scholar 

  10. Epstein MA, Achong YM, Barr Y, Zajac, B, Henle G, Henle W (1966) Morphological and virological investigations on cultured Burkitt tumor lymphoblasts (strain Raji) J Natl Cancer Inst 37:347

    Google Scholar 

  11. Falkoff RJM, Muraguchi A, Hong JX, Butler JL, Dinarrello CA, Fauci AS (1983) The effects of interleukin 1 on human B cell activation and proliferation. J Immunol 131:801

    Google Scholar 

  12. Farrar JJ, Fieller-Farrar J, Simon PL, Hilfiker ML, Stadler BM, Farrar WL (1980) Thymoma production of T cell growth factor (Interleukin 2) J Immunol 125:2555

    Google Scholar 

  13. Ford RJ, Mihta SR, Franzini D, Montagna R, Lachman LB, Maizel AL (1981) Soluble factor activation of human B lymphocytes. Nature 294:261

    Google Scholar 

  14. Gerber P, Hoyer B (1971) Induction of cellular DNA synthesis in human leukocytes by Epstein Barr virus. Nature 231:46

    Google Scholar 

  15. Gordon J, Levy SC, Melamed MD, Aman P, Hughes-Jones, NC (1984) Soluble factor requirements for the autostimulatory growth of B lymphoblasts immortalized by Epstein-Barr virus. J Exp Med 159:1554

    Google Scholar 

  16. Gordon J, Levy SC, Melamed MD, English LS, Hughes-Jones NC (1984) Immortalized B lymphocytes produce B-cell growth factor. Nature 30:154

    Google Scholar 

  17. Griffin BE, Kavian L (1984) Immortalization of monkey epithelial cells by specific fragments of Epstein-Barr virus DNA Nature 399:78

    Google Scholar 

  18. Howard M, Mizel SB, Lachman L, Ansel J, Johnson B, Paul WE (1983) Role of interleukin 1 in anti-immunoglobulin induced B cell proliferation. J Exp Med 157:1529

    Google Scholar 

  19. Issekutz T, Chu E, Geha RS (1982) Antigen presentation by human B cells: T cells proliferation induced by Epstein Barr Virus B lymphoblastoid cells. J Immunol 129:1446

    Google Scholar 

  20. Klein E, Klein G, Nadkarni S, Wigzell H, Clifford P (1968) Surface IgM-kappa specificity on a Burkitt lymphoma cell in vivo and in derivied cultures lines. Cancer Res 28:1300

    Google Scholar 

  21. Klein G, Giovanella B, Westman A, Stehlin J, Mumford D (1976) An EBV-genome negative cell line established from an American Burkitt lymphoma; receptor characteristics, EBV infectibility, and permanent conversion into EBV-positive sublines by in vitro infection. Intervirology 5:319

    Google Scholar 

  22. Leuthard P, Steck G, Burk R, Otto A (1980) Two different growth factors from an SV40 transformed BHK cell lines stimulate both migration and DNA synthesis. In: Jimenez de Asua, Levi-Montalcini, Shields Incobelli (eds.). Control mechanisms in animal cells, Raven Press New York pp 259

    Google Scholar 

  23. Lipsky PE, Thompson PA, Rosenwasser LJ, Dinarello CA (1983) The role of interleukin 1 in human B cell activation: inhibition of B cell proliferation and the generation of immunoglobulin-secreting cells by an antibody against human leukocytic pyrogen. J Immunol 130:2708

    Google Scholar 

  24. Rosen A, Gergely P, Jondal M, Klein G, Britton S (1977) Polyclonal Ig production after Epstein-Barr virus infection of human lymphocytes in vitro. Nature 267:52

    Google Scholar 

  25. Sanderson R, Vesole D, Jakway J, Talmage D (1980) A lymphocyte growth factor made by human lymphoid cell lines. Immunol Rev 51:177

    Google Scholar 

  26. Scala G, Kuang YD, Hall RE, Muchmore AV, Oppenheim JJ (1984) Accessory cell function of human B cells. 1. Production of both interleukin 1-like activity and an interleukin 1 inhibitory factor by an EBV-transformed human B cell line. J Exp Med 159:1637

    Google Scholar 

  27. Todaro GL, DeLarco JE, Marquardt H, Bryant M, Sherwin SA, Sliske AH (1979) Polypeptide growth factors produced by tumor cells and virus transformed cells: a possible growth advantage for the producer cells. Cold Spring Harbor Conference Cell Proliferation 6:113

    Google Scholar 

  28. Twardzik DR, Todaro GJ, Marquardt H, Reynolds FH, Stephenson JR (1982) Transformation induced by Abelson murine leukemia virus involves production of a polypeptide growth factor. Science 216:894

    Google Scholar 

  29. Waterford MD, Scrace GT, Whittle N, Stroobant P, Johnsson A, Wasteson A, Westermark B, Heldin CH, Huang JS, Deuel TF (1983) Platelet-derived growth factor is structurally related to the putative transforming protein p28SIS of simian sarcoma virus. Nature 304:38

    Google Scholar 

  30. Yoshida T, Kuratsiyi A, Takada A, Takada Y, Minowada J, Cohen S (1976) Lymphokine-like factors produced by human lymphoid cell lines with B or T cell surface markers. J Immunol 117:548

    Google Scholar 

  31. Zajac BA, Henle W, Henle G (1969) Autogenous and virus induced interferons from lines of lymphoblastoid cells. Cancer Res 29:1467

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by grants from the Concern Foundation and the Brigham Surgical Foundation

Rights and permissions

Reprints and permissions

About this article

Cite this article

Blazar, B.A., Sutton, L.M. & Strome, M. Immunomodulating activity in supernatants from EBV immortalized lymphocytes. Cancer Immunol Immunother 22, 62–67 (1986). https://doi.org/10.1007/BF00205718

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00205718

Keywords

Navigation